Investigating the role of miRNA-378-3p and its target PDIA-4 in endothelial cells
Abstract
Endothelial cells (ECs) line the innermost layer of blood vessels and maintain vascular homeostasis. Endothelial dysfunction may lead to cardiovascular diseases (CVDs) such as atherosclerosis. Autophagy maintains cellular homeostasis by degrading and recycling unused proteins for its’ reuse. Impaired endothelial autophagy is reported in CVDs. MicroRNAs are non-coding RNAs which regulate autophagy and endothelial function. However, the exact role of miRNA in endothelial autophagy and function is unknown. To this aim, we identified miR-378-3p as the most upregulated miRNA in autophagy-deficient ECs via miRNA-array. Inhibition and activation of autophagy up- and down-regulated miR-378-3p expression, respectively. MiR-378a-3p overexpression or inhibition inversely correlated with autophagy and function in ECs. Protein Disulfide Isomerase-4 (PDIA-4) was identified as the miR-378-3p target, where loss of PDIA-4 promoted TGFβ-mediated endothelial to mesenchymal transition. The novel identified relationship between MiR-378a-3p, endothelial autophagy and function can be used to modulate/improve endothelial autophagy and function to treat CVDs in the future.